[논문]시호 물 추출물의 마우스 골수세포를 이용한 유전독성 평가

전우현; 정인권; 강수진; 구세광; 이영준

시호 물 추출물의 마우스 골수세포를 이용한 유전독성 평가
Micronucleus Test of Bupleuri Radix Aqueous Extract in Bone Marrow Cells of Male ICR Mice 원문보기

韓國韓醫學硏究院論文集 = Korean journal of oriental medicine, v.18 no.2 = no.35, 2012년, pp.151 - 157

전우현 (대구한의대학교 한의과대학) , 정인권 (대구한의대학교 한의과대학) , 강수진 (대구한의대학교 방제과학 글로벌 연구센터) , 구세광 (대구한의대학교 한의과대학) , 이영준 (대구한의대학교 한의과대학)

Abstract ▼ AI-Helper

In this research, the genotoxic effect of Bupleuri Radix (BR), the dried roots of Bupleurum falcatum Linne has been traditionally used as anti-inflammatory agent, was evaluated using the mouse micronucleus test. BR aqueous extract (yield = 16.52%) was administered once a day for 2 continuous days by oral gavage to male ICR mice at doses of 2,000, 1,000 and 500 mg/kg. Cyclophosphamide (CPA) 70 mg/kg was used as a known genotoxic agent in a positive control. The appearance of a micronucleus (MN) in polychromatic erythrocyte (PCE) is used as an index for genotoxic potential, and PCE ratio is used as an index of cytotoxicity. Although significant (p<0.01) increase of the number of PCE with one or more nuclei (MNPCE) was detected in CPA treated groups, no significant increases of MNPCE numbers were observed in all three different dosages of BR extracts treated mice with over 0.30 of the individual polychromatic erythrocyte ratio in all mice used in this study. The results obtained indicated that BR extract shows no genotoxicity effects up to 2,000 mg/kg dosing levels the limit dosage in rodents.

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제안 방법

. The procedure is based on the observation that mitotic cells with chromatid breaks or incomplete exchanges or with malfunction of the spindle apparatus suffer from disturbances in anaphase distribution of their chromatin. After telophase, a sizable portion of this displaced chromatin is not included in the nuclei of the daughter cells but forms single or multiple micronuclei in the cell cytoplasm.
BR extracts were stored in a refrigerator at -20℃ to protect from light and degeneration, and they are well soluble upto 200 mg/ml concentration levels in distilled water used as vehicle as clear light brown solution. The test article was orally administered at a dosage volume of 10 ml/kg, once a day for 2 days by oral gavage to mice; total 2,000, 1,000 and 500 mg/kg using distilled water as vehicle. Cyclophosphamide․H2O (CPA; Sigma, USA) was used as an identified genotoxic agents in a positive control group.

대상 데이터

The animals were allocated into five groups 7 mice each. The fixed highest dosage level of 2,000 mg/kg oral dosing was chosen in accordance to the KFDA guidelines⁴⁾, the limited highest dosage in rodent, and 1,000 and 500 mg/kg was selected using the common ratio 2.
Thirty-five male ICR mice (6-wk old upon receipt, SLC, Japan) were used after acclimatization for 10 days. The body weights of animals at receipt are ranged in 28~32 g.
Animals were marked by picric acid. This study was carried out according to the guidelines of the Animal Ethical Committee, The University of Daegu Haany University (Gyeongsan, Korea).

이론/모형

Multiple comparison tests for different dose groups were conducted. Variance homogeneity was examined using the Levene test²¹⁾. If the Levene test indicated no significant deviations from variance homogeneity, the obtain data were analyzed by one way ANOVA test followed by the Scheffe test to determine which pairs of group comparison were significantly different.

성능/효과

Although significant (p<0.01) decreases of the mean PCE numbers and ratio were detected in CPA treated mice as compared with negative control, the mean PCE ratio in total 1000 erythrocytes was detected above 0.35 (in individual mice, over 0.30) in all tested groups including negative and positive control (Fig 1, Table 2).
Although significant (p<0.01) decreases of the mean PCE numbers and ratio were detected in CPA treated mice as compared with negative control, the mean PCE ratio was detected as over 0.35 in all tested groups including negative and positive control in the present study.
Based on the results, it is concluded that BR extract shows no genotoxicity effects up to 2,000 mg/kg dosing levels. In addition, it is also considered that there were no problems from cytotoxicity of BR extract because the mean PCE ratio was estimated over 0.
In the present study, CPA used as a positive control, and it showed a significant increases of MNPCE ratios. This indicates that the experiment protocol and the results of the present study are acceptable, and no meaningful increases of MNPCE were reported up to 2,000 mg/kg of BR extract.

후속연구

However, there are no reports dealing the potential genotoxicity of BR extract upon our knowledge. The objective of the present study, therefore, was to obtain the genotoxic information about BR aqueous extracts, and further clarify their safety for clinical use.

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